[unreadable] The mission of the Children's Oncology Group (COG) Phase 1/Pilot Consortium is to identify and develop effective new agents for children and adolescents with cancer, through rational and efficient clinical and laboratory research. Consortium clinical trials employ correlative pharmacological, biologic, and imaging studies to further the understanding of the disposition and action of new agents introduced into the treatment of children with cancer. [unreadable] [unreadable] The Consortium's primary specific aims are as follows: 1) To perform phase 1 trials of agents that target specific tumor types based on available data from tumor model systems, known molecular targets, and adult clinical trial data. 2) To develop agents that have additive or synergistic activity when combined with current cytotoxic chemotherapeutic agents, that modulate the antitumor or toxic effects of conventional anticancer drugs, or that provide a more efficacious or less toxic alternative to current chemotherapeutic agents. 3) To perform pilot trials that incorporate novel agents or combinations of agents, or that incorporate pharmacologic or biologic endpoints to enhance our understanding of the new agents and their effect on the tumor, in selected tumor types based on available data from tumor model systems, the molecular profile of the tumor, and pediatric phase 1 and 2 trial data. [unreadable] [unreadable] Advances made in the treatment of childhood malignancies over the past four decades have resulted in overall cure rates of approximately 80%. Despite these advances, several childhood cancers still have unacceptably low cure rates. Furthermore, even when treatment is successful, the acute and long-term morbidity of current therapy can be substantial. Agents targeting critical signaling pathways in the malignant process now have an established role in the treatment of select adult cancers. Development of targeted therapy for childhood cancer offers the prospect of more efficacious and less toxic therapeutics. [unreadable]